[Federal Register Volume 85, Number 76 (Monday, April 20, 2020)]
[Notices]
[Pages 21855-21858]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-08331]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Safety of Vaccines Used 
for Routine Immunization in the United States

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for Supplemental Evidence and Data Submissions

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SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from the public. Scientific 
information is being solicited to inform our review on Safety of 
Vaccines Used for Routine Immunization in the United States, which is 
currently being conducted by the AHRQ's Evidence-based Practice Centers 
(EPC) Program. Access to published and unpublished pertinent scientific 
information will improve the quality of this review.

DATES: Submission Deadline on or before 30 days after the date of this 
publication in the Federal Register.

ADDRESSES: 
    Email Submissions: [email protected].
    Print Submissions:
    Mailing Address: Center for Evidence and Practice Improvement; 
Agency for Healthcare Research and Quality, ATTN: EPC SEADs 
Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857.
    Shipping Address (FedEx, UPS, etc.): Center for Evidence and 
Practice Improvement; Agency for Healthcare Research and Quality, ATTN: 
EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, 
MD 20857.

FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301-427-1496 
or Email: [email protected].

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned the Evidence-based Practice Centers (EPC) 
Program to complete a review of the evidence for Safety of Vaccines 
Used for Routine Immunization in the United States. AHRQ is conducting 
this systematic review pursuant to Section 902(a) of the Public Health 
Service Act, 42 U.S.C. 299a(a).
    The EPC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for each of its reviews. In 
order to do so, we are supplementing the usual manual and electronic 
database searches of the literature by requesting information from the 
public (e.g., details of studies conducted). We are looking for studies 
that report on Safety of Vaccines Used for Routine Immunization in the 
United States, including those that describe adverse events. The entire 
research protocol is available online at: https://effectivehealthcare.ahrq.gov/products/safety-vaccines/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Safety of Vaccines Used for Routine 
Immunization in the United States helpful:
    [ssquf] A list of completed studies that your organization has 
sponsored for this indication. In the list, please indicate whether 
results are available on ClinicalTrials.gov along with the 
ClinicalTrials.gov trial number.
    [ssquf] For completed studies that do not have results on 
ClinicalTrials.gov, a summary, including the following elements: study 
number, study period, design, methodology, indication and diagnosis, 
proper use instructions, inclusion and exclusion criteria, primary and 
secondary outcomes, baseline characteristics, number of patients 
screened/eligible/enrolled/lost to follow-up/withdrawn/analyzed, 
effectiveness/efficacy, and safety results.
    [ssquf] A list of ongoing studies that your organization has 
sponsored for this indication. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, the 
protocol for the study including a study number, the study period, 
design, methodology, indication and diagnosis, proper use instructions, 
inclusion and exclusion criteria, and primary and secondary outcomes.
    [ssquf] Description of whether the above studies constitute ALL 
Phase II and above clinical trials sponsored by your organization for 
this indication and an index outlining the relevant information in each 
submitted file.
    Your contribution is very beneficial to the Program. Materials 
submitted must be publicly available or able to be made public. 
Materials that are considered confidential; marketing materials; study 
types not included in the review; or information on indications not 
included in the review cannot be used by the EPC Program. This is a 
voluntary request for information, and all costs for complying with 
this request must be borne by the submitter.
    The draft of this review will be posted on AHRQ's EPC Program 
website and available for public comment for a period of 4 weeks. If 
you would like to be notified when the draft is posted, please sign up 
for the email list at: https://www.effectivehealthcare.ahrq.gov/email-updates.
    The systematic review will answer the following questions. This 
information is provided as background. AHRQ is not requesting that the 
public provide answers to these questions.

Key Questions (KQ)

    KQ 1: What is the evidence that vaccines included in the 
immunization schedule recommended for adults in the United States 
(https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html) are safe in 
the short term (within 42 days following immunization) or long term 
(>42 days after immunization)?

[[Page 21856]]

    KQ1a. What adverse events (AEs) are collected in clinical studies 
(Phases I-IV) and in observational studies containing a control/
comparison group?
    KQ1b. What AEs are reported in clinical studies (Phases I-IV) and 
in observational studies containing a control/comparison group?
    KQ1c. What AEs are associated with these vaccines?
    1. For each AE associated with a particular vaccine, what is the 
average severity and frequency?
    2. For AEs without statistically significant associations with a 
particular vaccine, what is the range of possible effects?
    3. For each AE associated with a particular vaccine, what are the 
risk factors for the AE (including age, sex, race/ethnicity, genotype, 
underlying medical condition, whether a vaccine is administered 
individually or in a combination vaccine product, schedule of vaccine 
administration, adjuvants, and medications administered concomitantly)?
    KQ 2: What is the evidence that vaccines included in the 
immunization schedules recommended for children and adolescents in the 
United States (https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html) are safe in the short term (within 42 days following 
immunization) or long term (>42 days after immunization)?
    KQ2a. What AEs are collected in clinical studies (Phases I-IV) and 
in observational studies containing a control/comparison group?
    KQ2b. What AEs are reported in clinical studies (Phases I-IV) and 
in observational studies containing a control/comparison group?
    KQ2c. What AEs are associated with these vaccines?
    1. For each AE associated with a particular vaccine, what is the 
average severity and frequency?
    2. For AEs without statistically significant associations with a 
particular vaccine, what is the range of possible effects?
    3. For each AE associated with a particular vaccine, what are the 
risk factors for the AE (including age, sex, race/ethnicity, genotype, 
underlying medical condition, whether a vaccine is administered 
individually or in a combination vaccine product, schedule of vaccine 
administration, adjuvants, and medications administered concomitantly)?
    KQ 3: What is the evidence that vaccines recommended for pregnant 
women in the United States are safe in the short term (within 42 days 
following immunization) or long term (>42 days after immunization) for 
both the woman and her fetus/infant?
    KQ3a. What AEs are collected in clinical studies (Phases I-IV) and 
in observational studies containing a control/comparison group?
    KQ3b. What AEs are reported in clinical studies (Phases I-IV) and 
in observational studies containing a control/comparison group?
    KQ3c. What AEs are associated with these vaccines?
    1. For each AE associated with a particular vaccine, what is the 
average severity and frequency?
    2. For AEs without statistically significant associations with a 
particular vaccine, what is the range of possible effects?
    3. For each AE associated with a particular vaccine, what are the 
risk factors for the AE (including age, sex, race/ethnicity, genotype, 
underlying medical condition, whether the vaccine is administered 
individually or in a combination vaccine product, the schedule of 
vaccine administration, adjuvants, and medications administered 
concomitantly)?
    KQ3d. What AEs are associated with these vaccines in the fetus/
infant?
    1. For each AE associated with a particular vaccine, what is the 
average severity and frequency?
    2. For AEs without statistically significant associations with a 
particular vaccine, what is the level of certainty?
    3. For each AE associated with a particular vaccine, what are risk 
factors for the AE (including age, gender, race/ethnicity, genotype, 
underlying medical condition, whether vaccine administered individually 
or in a combination vaccine product, vaccine schedule of 
administration, adjuvants, medications administered concomitantly)?

                  PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, Settings)
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               Domain                              Inclusion                              Exclusion
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Population.........................   Human participants of all      Studies in animals or
                                      ages for whom the vaccines are         mechanistic/in vitro studies.
                                      recommended in the United States.      Studies exclusively in
                                                                             populations for whom the vaccine is
                                                                             not approved or is contraindicated.
Interventions......................  All KQs..............................   Studies of vaccines not on
                                      Individual vaccines included   the United States recommended
                                      in the immunization schedule           schedules, including brands/
                                      recommended for adults, children and   formulations not available in the
                                      adolescents, and pregnant women, as    United States, or no longer used.
                                      well as combination vaccines
                                      available in the United States..
                                     Vaccines for adults (KQ1)............

[[Page 21857]]

 
                                         Hepatitis A (HepA;
                                         Havrix, Vaqta); hepatitis B
                                         (HepB; Engerix-B, Recombivax HB,
                                         HEPLISAV-B); HepA-Hep B
                                         (Twinrix); Haemophilus influenzae
                                         type b (Hib; PedvaxHIB, ActHIB,
                                         Hiberix); human papillomavirus
                                         (HPV, HPV9; Gardasil 9);
                                         inactivated influenza (IIV;
                                         Afluria Quadrivalent, Flucelvax
                                         Quadrivalent, Fluarix
                                         Quadrivalent, Flulaval
                                         Quadrivalent, Fluzone High Dose,
                                         Fluzone Quadrivalent, Fluad);
                                         live attenuated influenza (LAIV;
                                         FluMist Quadrivalent);
                                         recombinant influenza (RIV;
                                         Flublok Quadrivalent); measles,
                                         mumps, rubella (MMR; M-M-R II);
                                         meningococcal (Menactra [MenACWY-
                                         D], Menveo [MenACWY-CRM]);
                                         Meningococcal B (MenB; Bexsero
                                         [MenB-4C], Trumenba [MenB-FHbp]);
                                         pneumococcal conjugate vaccine
                                         (PCV13; Prevnar 13); pneumococcal
                                         polysaccharide vaccine (PPSV23;
                                         Pneumovax); tetanus, diphtheria,
                                         & acellular pertussis (Tdap;
                                         Adacel, Boostrix); tetanus,
                                         diphtheria (Td; TDVAX, Tenivac);
                                         varicella (VAR; Varivax); zoster
                                         (recombinant, RZV; live, ZVL;
                                         Shingrix, Zostavax).
                                     Children and Adolescents (KQ 2)......
                                         Vaccines for children and
                                         adolescents will include
                                         diphtheria, tetanus, & acellular
                                         pertussis (DTaP; Daptacel,
                                         Infanrix); hepatitis A (HepA;
                                         Havrix, Vaqta); hepatitis B
                                         (HepB; Engerix-B, Recombivax HB);
                                         Haemophilus influenzae type b
                                         (Hib; PedvaxHIB, ActHIB,
                                         Hiberix); human papillomavirus
                                         (HPV, HPV9; Gardasil 9);
                                         inactivated polio vaccine (IPV;
                                         IPOL); inactivated influenza
                                         (IIV; Afluria Quadrivalent,
                                         Fluarix Quadrivalent, Flulaval
                                         Quadrivalent, Fluzone
                                         Quadrivalent, Flucelvax
                                         Quadrivalent); live attenuated
                                         influenza (LAIV; FluMist
                                         Quadrivalent); measles, mumps,
                                         rubella (MMR; M-M-R II);
                                         meningococcal (MenACWY-D, Men-
                                         ACWY-CRM; Menactra [MenACWY-D],
                                         Menveo [MenACWY-CRM]);
                                         meningococcal B (MenB; Bexsero
                                         [MenB-4C], Trumenba [MenB-FHbp]);
                                         pneumococcal conjugate vaccine
                                         (PCV13; Prevnar 13); pneumococcal
                                         polysaccharide vaccine (PPSV23;
                                         Pneumovax); rotavirus (RV;
                                         Rotarix, RotaTeq); tetanus,
                                         diphtheria, & acellular pertussis
                                         (Tdap; Adacel, Boostrix);
                                         varicella (VAR; Varivax); DTaP-
                                         HepB-IPV (Pediarix); DTaP-IPV/Hib
                                         (Pentacel); DTaP-IPV (Kinrix,
                                         Quadracel); MMR-V (ProQuad); DTaP-
                                         IPV-Hib-HepB (Vaxelis).
                                     Vaccines for pregnant women (KQ3)....
                                         Hepatitis B (HepB;
                                         Engerix-B, Recombivax HB,
                                         HEPLISAV-B); inactivated
                                         influenza (IIV; Afluria
                                         Quadrivalent, Flucelvax
                                         Quadrivalent, Fluarix
                                         Quadrivalent, Flulaval
                                         Quadrivalent, Fluzone
                                         Quadrivalent); recombinant
                                         influenza (RIV; Flublok
                                         Quadrivalent); tetanus,
                                         diphtheria, & acellular pertussis
                                         (Tdap; Adacel, Boostrix).
Comparators........................   Active comparators (e.g.,      Studies without
                                      other vaccines or other vaccination    intervention comparator.
                                      schedules) and inactive comparators
                                      (e.g., no vaccine).
Outcomes...........................   Adverse events identified in   Studies reporting only on
                                      participants, and, in the case of      effectiveness outcomes.
                                      pregnant women, in their fetuses/
                                      infants (including the presence and
                                      the absence of harms, toxicities,
                                      transient side effects, and
                                      unintended adverse health effects).
Timing.............................   Short term (within 30-42       No exclusions apply.
                                      days following immunization) as well
                                      as long term (>42 days after
                                      immunization) effects.
Setting(s).........................   No restrictions with regard
                                      to settings.
Study design.......................   Controlled studies             Studies without comparator
                                      (randomized and non-randomized         (e.g., case studies *).
                                      controlled clinical trials, cohort
                                      studies comparing two or more
                                      cohorts, case-control studies, self-
                                      controlled case series).
Other limiters.....................   English language scientific    Studies published in
                                      journal publications and trial         abbreviated form only (e.g.,
                                      records with published results.        letters, conference abstracts).
                                                                             Studies reported only in
                                                                             non-English publications.
----------------------------------------------------------------------------------------------------------------
* Case studies are outside the scope of the review because they do not include unvaccinated individuals for
  comparison.



[[Page 21858]]

    Dated: April 15, 2020.
Virginia Mackay-Smith,
Associate Director, Office of the Director, AHRQ.
[FR Doc. 2020-08331 Filed 4-17-20; 8:45 am]
BILLING CODE 4160-90-P